Neurogenesis During Pregnancy Influences Maternal Behavior
Post by Laura Maile
The takeaway
Adult neural stem cells (NSCs) contribute to brain plasticity throughout life. During different phases of pregnancy, NSCs differentiate into distinct subtypes of olfactory bulb neurons, influencing maternal behavior.
What's the science?
The adult mouse brain contains stem cells that are influenced by environmental changes and can differentiate into distinct cell types. Physiological states such as hunger and satiety are known to influence specific regional populations of adult NSCs. Pregnancy induces changes in several brain areas including the ventricular subventricular zone (V-SVZ), which contains neural stem cells (NSCs) that differentiate into olfactory bulb neurons and show increased proliferation at certain stages of pregnancy. It’s unknown, however, whether pregnancy and other physiological states can control specific populations of NSCs and whether there’s a functional outcome on brain plasticity and behavior. This week in Science, Chaker and colleagues investigated how distinct neural stem cells respond to pregnancy to produce specific olfactory bulb neurons that influence the behavior of mothers around the time of birth.
How did they do it?
Using GFAP and Ki67 in mice, the authors labeled and quantified proliferating NSCs in the V-SVZ on different days of gestation and post-pregnancy. Next, they injected pregnant females with a thymidine analog on specific days of pregnancy to label newly born neurons and then analyzed their olfactory bulbs three weeks later when the labeled neurons would be integrated. This allowed them to determine whether specific populations of NSCs differentiate into distinct cell layers and subtypes of olfactory bulb neurons. To understand whether the newly differentiated olfactory bulb neurons were long-lasting past weaning (i.e., when the mice are separated from the mother), they quantified the surviving cells again 30 days post analog injection. They next performed spatial transcriptomics to characterize the genetic profiles of olfactory bulb layers that experience neurogenesis (i.e., growth of new neurons) during and after pregnancy. They then focused on one cluster that was enriched in mothers during pregnancy to determine what neuronal markers were associated with pregnancy. To determine the function of the transiently increased pregnancy-associated neurons, the authors measured their survival when maternal care was disrupted by prematurely removing pups, cross-fostering with new pups, or exposing mothers or virgin mice to pup nest odor. Finally, they conducted olfactory behavior tests in mothers during pregnancy who had specific populations of olfactory bulb interneurons depleted or maintained.
What did they find?
The authors discovered that distinct regions of the V-SVZ showed activity and proliferation on specific days during pregnancy. This indicates that there are both temporally and spatially dynamic patterns of differentiation controlled by the phase of pregnancy of the adult mouse. After injecting a thymidine analog on specific gestation days, they found that pregnancy induces neurogenesis in discrete sublayers of the olfactory bulb and that these new neurons become functionally integrated into the existing circuitry. Once pups began feeding on solid food and required less maternal care, however, the olfactory bulb showed decreased numbers of these newborn neurons, and nearly all of them disappeared by weaning. This confirms that pregnancy induces transient neurogenesis at specific stages of the perinatal period. Spatial transcriptomics revealed clusters of neurons corresponding to olfactory bulb layers, that showed upregulation in certain genes at specific time points, indicating the spatial and temporal control of neurogenesis in response to pregnancy.
When pups were removed from maternal care prematurely, certain interneurons were correspondingly lost early. Similarly, when cross-fostering with news pups, some pregnancy-related interneurons survived, while others were lost. The neurons lost shared genetic profiles and location in olfactory layers. Additionally, specific interneuron populations were rescued when mothers were exposed to new pup nest odor, and others were not, indicating the necessity of pup odor for the survival of pregnancy-related neurons. Loss of one type of pregnancy-related interneuron reduced the ability of mothers to discriminate between their own pups and new pups. This shows that pregnancy-related neurogenesis is important for own pup odor recognition, but not for general olfactory function. Loss of different types of interneurons decreased pup exploration index, suggesting that pregnancy-related neurogenesis is important for pup odor sensitivity during early motherhood.
What's the impact?
This study demonstrated that neural stem cells can generate specific populations of neurons to help pregnant mothers prepare for maternal care. Different physiological states, such as hunger, satiety, and pregnancy, can influence adult neurogenesis to suit transient needs and influence behavior, according to environmental and physiological changes.